Much is known of the anatomy and chemistry of opiate systems involved in analgesia, although the manner in which neural systems interact to mediate nociception and analgesia is still unclear. This is particularly true of the Kappa opiate mediated analgesia. The experiments proposed here will study the role of Kappa and Mu receptors in nociception and analgesia in the preweanling rat. Preliminary data demonstrated that the ontogeny of Kappa receptors measured biochemically preceded that of Mu receptors, and that ketocyclazocine (KC) produced analgesia 2-4 days earlier than morphine did to a thermal nociceptive stimulus to the tail of the pup. The onset of KC induced analgesia paralleled the development of Kappa receptor while the onset of morphine induced analgesia paralleled that of Mu receptor. These data provide a model for the in vivo study of Kappa receptor function in analgesia. The experiments proposed adhere will confirm and extend these findings. The maturation of the Mu receptor will be defined biochemically in whole brain and spinal cord by receptor binding studies using the Mu and Delta blockers, normorphine and DADLE, to characterize the Kappa site. Pharmacological studies will define: the ability of these drugs to produce analgesia to a mechanical nociceptive stimulus; the ability of naloxone, which in vitro is a more potent Mu antagonist than Kappa antagonist, to block KC and morphine induced analgesia; and study the development of tolerance and cross-tolerance with these two drugs. Further studies will begin to define the anatomical sites of action of KC and morphine by testing for an analgesia induced by these two opiates in spinal sectioned pups and by local injection of KC and morphine intraspinally. Finally, autoradiographic studies of the Kappa receptor in spinal cord will be initiated to detail the anatomical and biochemical substrates of Kappa opiate induced analgesia. The understanding of the role of these receptor mechanisms in analgesia may lead to the development of narcotics that have more specific actions, and fewer unwanted side effects, including addictive properties.